Co-enzyme Q10 (CoQ10) is a co-enzyme; a substance in the body that assists the function of an enzyme or enzyme system. CoQ10 was discovered in 1957, and its molecular structure was determined in 1958 to be 2,3-dimethoxy-5-methyl-6-decaprenil-1,4-benzoquinone. Its biological presence was ubiquitously found in the body and because of its ubiquitous nature, CoQ10 came to be known as ubiquinone. CoQ10 exists in at least 3 distinct chemical entities; ubiquinol (reduced state product), semiquinone radical (1-electron oxidation product), and ubiquinone (2-electron oxidation product). Ubiquinone and ubiquinol are located on the inner membrane of the mitochondria, an intracellular organelle.
CoQ10 is a classic lipophilic antioxidant, like vitamin E. In an analogous fashion, vitamin E exists in the same 3 chemical identities as CoQ10; tocotrienol or tocopherol (reduced state product), chromanoxyl (i.e., tocotrienoxyl or tocopheroxyl) radical (1-electron oxidation product), and chromanoxyl quinone (2-electron oxidation product). This is exemplified in Table 1. Interestingly, CoQ10 and tocotrienol contain 10 and 3 isoprene units in their lipophilic tail, respectively.
TABLE 1IntermediateOxidized(1-electron(2-electronLipophilicReducedoxidation)oxidation)CompoundProductproductproductCo-enzyme Q10*UbiquinolSemiquinoneUbiquinoneradicalVitamin E (Chromanol)Tocotrienol (T3)*TocotrienolTocotrienoxylTocotrienoxylradicalquinoneTocopherol (T)TocopherolTocopheroxylTocopheroxylradicalquinone*CoQ10 and T3; their numeric designations indicate 10 and 3 repeating isoprene units, respectively.
Redox enzymes in the body are quite capable of interconverting ubiquinone to ubiquinol, and vice versa. For example, ubiquinone is the substrate for NADH dehydrogenase, and ubiquinol is the substrate for cytochrome c reductase. Similarly, there may be redox enzymes in the body that interconvert chromanoxyl quinone (vitamin E quinone) to chromanol (vitamin E), and vice versa. This is the biochemical and/or biological situation in vivo.
Chemically, ubiquinol is unstable (prone to oxidation), but chromanol is relatively more stable. Both of these lipid-soluble antioxidants are found embedded in membranes and in lipoprotein particles. Ascorbic acid and alpha-lipoic acid are known to protect vitamin E on the hydrophilic domain of the cytosolic membrane surfaces, converting any oxidized products back to the reduced alcohol products. However, in the lipid domain, ubiquinone-ubiquinol and tocopherol-tocotrienol protect lipid peroxidation, and they have only each other to interconvert within the lipid domain.
CoQ10 is critically needed for energy transduction and oxidative phosphorylation, so its role as an antioxidant is secondary. In the lipid domain, tocotrienol and tocopherol are the foremost and critical antioxidants. Both CoQ10 and vitamin E are carried in the phospholipids of lipoprotein particles throughout the arterial blood vessels, and there are 30,000 miles of these vessels throughout the body. Therefore, both vitamin E and CoQ10 are also delivered ubiquitously to many organs (e.g., heart, kidney, liver, pancreas, muscle, skin, plasma and adipose tissues).
CoQ10 in normal healthy adults is in the reduced ubiquinol form. This is the form our body requires for its metabolic utilization. Supplemental CoQ10 pills sold in stores are in the oxidized ubiquinone form. Normally, the body is capable of converting the oxidized ubiquinone form to the reduced ubiquinol form. Therefore, taking supplements of ubiquinone will suffice, since the healthy body reduces ubiquinone to ubiquinol. However, with age, oxidative stress and chronic inflammation, the body's ability to convert ubiquinone to ubiquinol is compromised (FIG. 1A). Supplemental ubiquinol are particularly useful to compensate for individuals with a reduced ability to convert ubiquinone to ubiquinol in the body.
Physiologically, the body reduces ubiquinone (a ketone) to ubiquinol (an alcohol), which is the active form of CoQ10 used during mitochondrial respiration. The addition of a vitamin E (e.g., tocotrienol) protects the labile oxidation of ubiquinol to ubiquinone, and furthermore, reduces ubiquinone to ubiquinol in situ (i.e., in softgels or other combinatory formulations) (FIG. 1B).
Physiologically, the body absorbs preformed vitamin A (retinol) or plant-derived intact beta-carotene and converts it to the useful form—retinol. Chemically, two molecules of retinol are in one molecule of beta-carotene. An enzyme in our body, beta-carotene deoxygenase, hydrolyses beta-carotene into two molecules of retinol. Vitamin A has many utilities, such as, cellular differentiation, immunity, skin health, and the most known use, sight. Retinol is the reduced state of vitamin A whereas retinoic acid is the oxidized state of vitamin A. Unlike the nontoxic CoQ10 couple, retinoic acid is toxic, and hence there is a cautionary limit to retinol consumption. The physiological role of retinoic acid in the body remains controversial or, at best, is uncertain. There have been some examples of the deleterious role of vitamin A (retinoic acid) in the body.
In preparation for lactation, expectant mothers store retinoids in the liver and breast. Breastfeeding allows the transfer of stored retinoids to infants for proper growth, immunity against pathogens, and sight in the world outside the womb. Thus, there is a natural process in place for reducing toxic accumulation of retinoids in mothers, averting hypervitaminosis A. It has been theorized that maternal hypervitaminosis A—primarily caused by a backup of retinoic acid—causes postpartum depression, a condition that affects 1 in 8 mothers.
Malaria is the most significant public health problem in the world with nearly 3.5 billion (1 in 2) people at risk. The malaria parasite absorbs vitamin A and converts it to retinoic acid for its use to invade the red blood cells. Listlessness from anemia in patients is the hallmark symptom of the disease. It has been theorized that hypervitaminosis A—from a backup of retinoic acid produced by the parasite—causes or exacerbates the symptoms in the person.
It is therefore understood that the oxidized form of vitamin A, retinoic acid, is detrimental. Furthermore, vitamin A in its reduced form (retinol) should be maintained for its essential functions in the body (FIG. 1C).